PMID- 12087098
OWN - NLM
STAT- MEDLINE
DCOM- 20021017
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 35
DP  - 2002 Aug 30
TI  - Regulation of ribosomal S6 kinase 2 by mammalian target of rapamycin.
PG  - 31423-9
AB  - Phosphorylation of the ribosomal S6 subunit is tightly correlated with enhanced 
      translation initiation of a subset of mRNAs that encodes components of the 
      protein synthesis machinery, which is an important early event that controls 
      mammalian cell growth and proliferation. The recently identified S6 kinase 2 
      (S6K2), together with its homologue S6K1, is likely responsible for the 
      mitogen-stimulated phosphorylation of S6. Like S6K1, the activation of S6K2 
      requires signaling from both the phosphatidylinositol 3-kinase and the mammalian 
      target of rapamycin (mTOR). Here we report the investigation of the mechanisms of 
      S6K2 regulation by mTOR. We demonstrate that similar to S6K1 the serum activation 
      of S6K2 in cells is dependent on mTOR kinase activity, amino acid sufficiency, 
      and phosphatidic acid. Previously we have shown that mTOR is a 
      cytoplasmic-nuclear shuttling protein. As a predominantly nuclear protein, S6K2 
      activation was facilitated by enhanced mTOR nuclear import with the tagging of an 
      exogenous nuclear localization signal and diminished by enhanced mTOR nuclear 
      export with the tagging of a nuclear export sequence. However, further increase 
      of mTOR nuclear import by the tagging of four copies of nuclear localization 
      signal resulted in its decreased ability to activate S6K2, suggesting that mTOR 
      nuclear export may also be an integral part of the activation process. 
      Consistently, the nuclear export inhibitor leptomycin B inhibited S6K2 
      activation. Taken together, our observations suggest a novel regulatory mechanism 
      in which an optimal cytoplasmic-nuclear distribution or shuttling rate for mTOR 
      is required for maximal activation of the nuclear S6K2.
FAU - Park, In-Hyun
AU  - Park IH
AD  - Department of Cell and Structural Biology, University of Illinois at 
      Urbana-Champaign, Urbana, Illinois 61801, USA.
FAU - Bachmann, Rebecca
AU  - Bachmann R
FAU - Shirazi, Haider
AU  - Shirazi H
FAU - Chen, Jie
AU  - Chen J
LA  - eng
GR  - GM58064/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020626
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Androstadienes)
RN  - 0 (Protein Subunits)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 8PJ61P6TS3 (1-Butanol)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - 1-Butanol/pharmacology
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Humans
MH  - Kidney
MH  - Kinetics
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - *Protein Serine-Threonine Kinases
MH  - Protein Subunits
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Recombinant Proteins/metabolism
MH  - Ribosomal Protein S6 Kinases/chemistry/*genetics
MH  - Ribosomes/enzymology
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Transfection
MH  - Wortmannin
EDAT- 2002/06/28 10:00
MHDA- 2002/10/18 04:00
CRDT- 2002/06/28 10:00
PHST- 2002/06/28 10:00 [pubmed]
PHST- 2002/10/18 04:00 [medline]
PHST- 2002/06/28 10:00 [entrez]
AID - S0021-9258(20)69989-6 [pii]
AID - 10.1074/jbc.M204080200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Aug 30;277(35):31423-9. doi: 10.1074/jbc.M204080200. Epub 2002 
      Jun 26.